Why Chloride Is Important For The Transport Of Negative Anions Across The Cell Membrane

Cystic Fibrosis (CF) is an autosomal recessive genetic disease that causes thickened mucus to form in the lungs, pancreas, and other organs. It affects a specific protein called Cystic Fibrosis Transmembrane Regulator (CFTR) that controls the normal movement of sodium, chloride, and water in and out of the cells within the body. Those diagnosed with CF have either too little or abnormal CFTR. When CFTR is absent or defective, the mucus usually secreted by the cells in the pulmonary airways, pancreatic ducts, and gastrointestinal tract become thickened, leading to obstructions, frequent infection, and loss of function in the affected organs (Cystic Fibrosis Symptoms, Causes & Risk Factors, 2018). According to the Cystic Fibrosis Foundation

The abnormality in the CFTR gene alters the CFTR protein in people with cystic fibrosis. As a result, one hallmark of CF is the presence of a thick mucus secretion which clogs the bronchial tubes in the lungs and plugs the exit passages from pancreas and intestines, leading to loss of function of these organs.

Cystic fibrosis is a hereditary disease of the secretory glands (National Heart, Lungs, and Blood Institute[NHLBI] , "What Is Cystic Fibrosis?", 2013). People who have cystic fibrosis inherit two defective genes, one from each parent (NHLBI , "What Is Cystic Fibrosis?", 2013). The body parts affected by cystic fibrosis are the lungs, pancreas, intestines, sinuses, and sex organs (NHLBI , "What Is Cystic Fibrosis?", 2013). The gene at fault for causing cystic fibrosis is the CFTR (cystic fibrosis transmembrane conductance regulator) gene (Genetics Home Reference, "CFTR gene", 2014). The transport of salts and chloride in and out of the cells is affected by the mutation of this gene (Cystic Fibrosis Research Inc., "About Cystic Fibrosis"). This disease most commonly affects Caucasians of North European descent (NHLBI , "What Is Cystic Fibrosis?", 2013).

The CF gene is found in Chromosome 7. Mutations in the CFTR gene cause cystic fibrosis. This protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells. Chloride is a component of sodium chloride, a common salt found in sweat. The official name of this gene is “cystic fibrosis transmembrane conductance regulator “or

Scientists have found more than 1,700 different mutations in the CFTR that can cause CF. Scientist have spent years trying to put these thousands of mutations into groups. They’re so many types of mutations but here are just some of them. Protein Production Mutations include splice mutations. These interfere with the production of the CFTR protein. IF the CFTR gene has a splice mutation the protein building instructions send a signal that causes the production of CFTR protein to stop. Gating Mutations is another mutation of CF. The CFTR protein is shaped like a tunnel with a gate. The cell can open the gate when chloride needs to flow through the channel. Otherwise, the gate stays closed. Mutations lock the gate in the closed position so that chloride cannot get

CF occurs through the inheritance of a loss-of-function mutation in the gene that encodes for the CF transmembrane conductance regulator (CFTR) membrane protein (2). This protein is a transporter responsible for actively transporting chloride ions and sodium ions, which in turn regulate osmotic balance (2). Mutations in CFTR affect the water-driving force in the epithelial surfaces lining the gastrointestinal tract and pancreas (2). This results in viscous and sticky mucus secretions which build on the epithelial surfaces (2). This environment causes patients with CF to be susceptible to

Cystic Fibrosis is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) which is located in the middle of chromosome 7. The CFTR gene encodes a protein of the same name. This protein functions as a “channel across the membrane of cells that produce mucus, sweat, saliva, tears and digestive enzymes” (Genetics Home Reference, 2015). The channel transports chloride ions which are negatively charged particles, in and out of cells which help in controlling the water movement in tissues to allow for the production of thin, feely flowing mucus, a substance that lubricates and lines the airways, digestive system, reproductive system and other tissues and

The discovery of therapeutic molecules that target the underlying cause of Cystic Fibrosis, rather than the symptoms, has transformed the approach of cystic fibrosis treatments. Two such sets of drugs are classed as correctors and potentiators. The latter set aim to target and augment the function of the mutated CFTR channel that is present on the membrane. Class III and IV CFTR mutations benefit from this approach as they are defined as mutated CFTR channels that, although present on the apical membrane, exhibit decreased, or no functional activity compared to functional CFTR channels. Class III mutations are missense mutations that result in a reduce open time of the CFTR channels. This severe class of mutations include G551D and S549R

Cystic Fibrosis is caused by a genetic defect in Chromosome 7. Chromosome 7 encodes the cystic fibrosis transmembrane conductance regulator, also known as CFTR. There are over 1,000 mutations of this gene causing cystic fibrosis, with each mutation manifesting as a different variation of disease onset and clinical presentation. The most common mutation is the loss of phenylalanine residue at deltaF508. The abnormal functioning CFTR causes impaired chloride transport and more viscous secretions. The defect causes dehydrated secretions in the respiratory tract and gastrointestinal tract. Being dehydrated, these secretions become more difficult to move throughout the body. Along with impaired mucociliary clearance, this leads to chronic infection and inflammation, which in turn leads to more impaired mucociliary clearance. It unfortunately becomes an endless

Cystic fibrosis (CF) is a progressive condition in which epithelial exocrine glands are obstructed (Howe, 2001). Whilst many organs and bodily systems are disrupted by CF, the lungs and gastrointestinal organs are predominantly affected; it is also most common amongst the Caucasian population due to the autosomal recessive gene (Quitter et al., 2003 cited in Wolfe & Mash, 2006, pg 514). The faulty gene effects the production of cystic fibrosis transmembrane conductance regulator protein, which is responsible for the formation of molecular tunnels which monitor the movement of salts and water from the cells (Hopkin, 2010 pg 4).

Most people have two working copies of the gene, but only one is needed to prevent CF. CF develops when neither copes can produce a functional CFTR protein. The CFTR gene tells cells in the body to produce proteins called CFTR proteins. These proteins act as pathways inside and outside of cells, which allows water and particles such as chloride ions to flow in and out of cells. This helps maintain a balance of salt and water. In those that have CFTR gene mutations the pathways don’t work correctly and what this means for people with the gene mutation is that those pathways don’t stay open long enough for chloride ions to flow through or they don’t open as often as they should. Water and salt cannot freely flow into and out of cells, the water and salt lead to thick, sticky mucus in the lungs as well as other parts of the

This protein is in charge of the movement of water and sodium ions through channels, giving substances like mucus a thick or thin concentration by moving the substances through the channels as needed (Cystic Fibrosis, 2015). Though it is known as a gene that can cause cystic fibrosis, it is not the only condition that can be a result of this mutation and if a mutation is found on this gene it is not a definite result that the child will have CF and will need further testing in order to determine what the physical manifestation of the mutation will be (Cystic Fibrosis,

People with this disease typically have higher levels of sodium and chloride concentrations than a person without the disease (Davies 2007). This is because of the missing gate of the chloride channel that the CFTR protein regulates, as described earlier. The most common organs to be affected by cystic fibrosis are the upper and lower air ways, reproductive tracts, pancreas, and bowel. In each organ, there is a buildup of mucus. By not being able to expel the mucus in the lungs, breathing becomes tougher and tougher and infections are very common (Ezzell, 1992).  A CF patient’s main problem is often with their lungs because they cannot effectively clear out the bacteria that has been inhaled. The immune system tries to fight this bacteria, but it ultimately causes a great inflammatory response. To compare just how bad the inflammation is, it is ten times more inflamed than a person with a lower respiratory tract infection (Davies,

Cystic Fibrosis (CF) is an autosomal recessive gene that causes a wide range of symptoms because there are over 1,000 changes or mutations that can occur within the cystic fibrosis transmembrane receptor (CFTR) protein. The CFTR protein is generally a chloride ion chain “regulated by cyclic adenosine monophosphate and therefore can act as a regulator of other electrolyte channels”(Grossman, S., & Grossman, L. 2005, p. 46). Typically this protein allows chloride ions to exit mucus-producing cells allowing water to flow in and thin the mucus. However, if the CFTR protein has been mutated, such as in cystic fibrosis, chloride ions cannot exit. This causes the mucus to thicken, become sticky, and obstruct the various channels it passes through. This build up of mucus also prevents bacteria from being cleaned from cells thoroughly increasing the patients risk for infections (Grossman, S., & Grossman, L. 2005). However, the severity of CF depends on whether the patients have complete or partial loss of the CFTR gene. If the person has the classic form of CF abnormalities of CFTR will commonly affect “…the respiratory, gastrointestinal, endocrine and metabolic, and genitourinary systems”(Schram, C. 2012). However, if people have atypical forms of CF their genetic disorder may only affect one of the organ systems and may not be found until the patient develops symptoms in their late childhood, early adolescence, or adulthood

Cystic Fibrosis is caused by a genetic defect in Chromosome 7. Chromosome 7 encodes the cystic fibrosis transmembrane conductance regulator, also known as CFTR. There are over 1,000 mutations of this gene causing cystic fibrosis, with each mutation manifesting as a different variation of disease onset and clinical presentation. The most common mutation is the loss of phenylalanine residue at deltaF508. The abnormal functioning CFTR causes impaired chloride transport and more viscous secretions. The defect causes dehydrated secretions in the respiratory tract and gastrointestinal tract. Being dehydrated, these secretions become more difficult to move throughout the body. Along with impaired